1. Field of the Invention
The present invention relates to a preparation process of polysuccinimide which is useful intermediate in a medicine and so on, and more particularly relates to a preparation process of high molecular weight polysuccinimide by heating aspartic acid in organic solvent and carrying out dehydration condensation.
2. Description of the Related Art
Generally polyamino acids are often used as a model compound of protein in the field of medicine and bio-chemistry. Polysuccinimide is a precursor in the synthesis of polyaspartic acid which is useful as an environmentally suitable and water soluble polymer, and additionally is a useful intermediate in the synthesis of pharmacologically valuable poly-(aspartic acid)-hydroxyalkylamide as disclosed in Japanese Patent Publication SHO 48-20638.
As to preparation of polysuccinimide, J. Amer. Chem. Soc., 80, 3361(1958) discloses a process for conducting heat condensation of aspartic acid at 200.degree. C. for 2.about.3 hours, however, the molecular weight of polysuccinimide obtained by the process is about 10,000. J. Org. Chem., 24, 1662(1959) discloses a process for conducting heat condensation of a derivative of maleic acid, malic acid or aspartic acid so as to prepare polysuccinimide having a molecular weight of 15,000 to 28,000. However, the process requires a step for synthesis of a derivative as a raw material. J. Org. Chem:, 26, 1084(1961) discloses a process for heating aspartic acid in tetralin for a long time, however, polysuccinimide obtained by the process has a low molecular weight and remarkable coloring.
U.S. Pat. No. 3,052,855 discloses a preparation process of a copolymer of aspartic acid copolymer or a glutamic acid in the presence of a phosphoric acid, and Japanese Patent Publication SHO 48-20638 discloses a process for carrying out the reaction in the form of a thin layer by using 85% phosphoric acid in a rotary evaporator to obtain high molecular weight polysuccinimide. Although any of these processes leads to polysuccinimide having a high molecular weight, it is disadvantageous to industrialize any of the processes, because the process leads to solidification of the reaction product and thus causes difficulty in stirring and isolating operations and additionally is very difficult to scale up. As a result, the process is unfavorable in industry.
Further, U.S. Pat. No. 4,363,797 discloses a process for conducting polymerization in a high boiling point solvent such as diphenyl ether in the presence of an ion exchange resin. However, polysuccinimide obtained by the process has a molecular weight of about 10,000.
As to a production process of polysuccinimide in industry, it has been known a process for conducting heat condensation in a fluid bed dryer (U.S. Pat. No. 5,057,597), a process for reacting maleic anhydride with ammonia and further heating with polysuccinimide (U.S. Pat. No. 5,219,952), and a process for dehydrating aspartic acid under reduced pressure (U.S. Pat. No. 5,219,986). However, polysuccinimide obtained by these processes has a molecular weight of about 10,000. A high molecular weight product cannot be obtained. U.S. Pat. No. 5,142,062 has described that high molecular weight polysuccinimide can be obtained by conducting heat condensation of aspartic acid under reduced pressure in the presence of a phosphoric acid, successively mechanical comminuting the reaction product and further conducting polymerization. However, the process causes solidification of the reaction product and leads to a problem of difficult operation.